Erowid References Database
de la Torre R, Farre M, Monks TJ, Jones D.
“Response to Sprague and Nichols: Contribution of metabolic activation to MDMA neurotoxicity”.
Trends in Pharmacological Sciences. 2005 Feb;26(2):60-61.
The letter by Sprague and Nichols  is a thoughtful contribution to the ongoing discussion of the complex mechanism of 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity. Our recent TiPS article  focused on one important aspect of the
PROBLEM: that is, the contribution of drug metabolism to neurotoxicity. This intentional approach, together with space constraints, limited a more extensive review of the neuropharmacology and neurotoxicology of ecstasy.
The fact that metabolic activation of MDMA is required to elicit a neurotoxic response has been reported by Esteban et al.  and others. In a previous study, Molliver and colleagues , after observing a lack of toxicity when MDMA was administered intracerebrally, concluded that the formation of a peripheral drug metabolite might be essential to induce neurotoxicity. These authors, in fact, expressed similar concerns to those of Sprague and Nichols, with respect to whether the duration of drug exposure via the intracerebral route was sufficient to activate all processes required to elicit neurotoxicity. Further experiments in which MDMA was infused into the brain for 48 h were performed subsequently, but the conclusion was the same. Similar conclusions have been reported by others.
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